Fusel oil

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

other information

Study period:

1999

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: A published study that is reported in sufficient detail to judge it as sufficiently reliable to add to the overall understanding of the toxicokinetics of this substance in humans.

Data source

Reference

Reference Type:

publication

Title:

Uptake of 10 polar solvents during short term respiration.

Author:

Kumagai S, Oda H, Matsunaga I, Kosada H, Akasaka S.

Year:

1999

Bibliographic source:

Tox Sci 48, 255-63

Materials and methods

Objective of study:

other: absorption elimination

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Measurement of the exhaled concentration of methanol (similar to ethanol) as a percentage of inhaled concentrations.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Methanol

EC Number:

200-659-6

EC Name:

Methanol

Cas Number:

67-56-1

Molecular formula:

CH4O

IUPAC Name:

Methyl alcohol

Details on test material:

no further information

Radiolabelling:

no

Test animals

Species:

human

Strain:

other: not applicable

Sex:

male

Details on test animals or test system and environmental conditions:

not applicable

Administration / exposure

Route of administration:

inhalation: vapour

Vehicle:

unchanged (no vehicle)

Details on exposure:

no further information

Duration and frequency of treatment / exposure:

10 minutes plus 5 minutes inhalation of clean air

Doses / concentrations

Remarks:

Doses / Concentrations:
100ppm

No. of animals per sex per dose / concentration:

4

Control animals:

no

Positive control reference chemical:

no

Details on study design:

no further information

Details on dosing and sampling:

no further information

Statistics:

no further information

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

See remarks on results below.

Metabolite characterisation studies

Metabolites identified:

no

Any other information on results incl. tables

The mean respiratory rate for each solvent was from 12.1 to 14 min^-1. The mean tidal volume was from 470 to 530 ml, no differences were found among the solvents. The results obtained with the different solvents suggests that the wash in/wash out behaviour cannot completely explain the actual respiratory behaviour of solvents such as methanol (ME).  The exhaled concentrations were between 25 (end exhaled) and 40% (start of exhale) of the inhalation concentration after 10 minutes of exposure, although the data did not show that a clear peak had been reached after this time.  The mean update over the last 5 minutes of respiration was 60.8%. The exhaled concentration fell to close to zero within the 5 minute recovery time. ME was not irritant to the eyes or respiratory tract at a dose of 100ppm for exposure periods of 10 minutes. Uptake of ethanol would be expected to be similar.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: Study not designed to assess bioaccumulation potential.
Methanol is readily absorbed by inhalation.

Executive summary:

A study investigated the respiratory uptake of methanol (a similar alcohol to ethanol) in male volunteers using a single exposure concentration of 100ppm and established that over a 10 minute period of exposure, uptake is around 61% of the inhaled concentration.  The authors concluded that the results of this study (which examined a number of solvents) when correlated with partition co-efficients supports the hypothesis that solvent absorbed in the mucous layer of the respiratory tract is removed by the bronchial blood circulation.